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- Hens, Bart, et al.
(författare)
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Formulation predictive dissolution (fPD) testing to advance oral drug product development : An introduction to the US FDA funded '21st Century BA/BE' project
- 2018
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 548:1, s. 120-127
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Forskningsöversikt (refereegranskat)abstract
- Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions.
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| 3. |
- Osaku, Erica F., et al.
(författare)
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beta-(1 -> 6)-d-glucan secreted during the optimised production of exopolysaccharides by Paecilomyces variotii has immunostimulatory activity
- 2018
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Ingår i: Antonie van Leeuwenhoek. International Journal of General and Molecular Microbiology. - : Springer. - 0003-6072 .- 1572-9699. ; 111:6, s. 981-994
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Tidskriftsartikel (refereegranskat)abstract
- Paecilomyces variotii is a filamentous fungus that occurs worldwide in soil and decaying vegetation. Optimization of the fermentation process for exopolysaccharide (EPS) production from the fungus P. variotii, structure determination and immuno-stimulating activity of EPS were performed. Response surface methodology (RSM) coupled with central composite design (CCD) was used to optimize the physical and chemical factors required to produce EPS in submerged fermentation. Preliminary investigations to choose the three factors for the present work were made using a factorial experimental design. Glucose, ammonium nitrate (NH4NO3) and pH were used as variables for which, with constant temperature of 28 A degrees C and agitation of 90 rpm, the optimal process parameters were determined as glucose values of 0.96%, NH4NO3 0.26% and pH 8.0. The three parameters presented significant effects. In this condition of culture, the main composition of the isolated EPS was a linear beta-(1 -> 6)-linked-D-glucan, as determined by Nuclear Magnetic Resonance (NMR) and methylation analysis. This polysaccharide is a very unusual as an EPS from fungi, especially a filamentous fungus such as P. variotii. Murine peritoneal macrophages cultivated with beta-glucan for 6 and 48 h showed an increase in TNF-alpha, IL-6 and nitric oxide release with increased polysaccharide concentrations. Therefore, we conclude that the beta-(1 -> 6)-linked-D-glucan produced in optimised conditions of P. variotii cultivation has an immune-stimulatory activity on murine macrophages.
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